The goal of this proposal is to better understand the respiratory-related behavior of the extrinsic tongue muscles, specifically those that protrude (genioglossus; GG) and retract (hyoglossus; HG) the tongue. Recent work in our laboratory has shown that co-activation of these antagonistic muscles improves pharyngeal airway patency. Obstructive sleep apnea (OSA) is a disorder marked by intermittent obstruction of the pharynx during sleep. This is commonly thought to be caused by passive prolapse of the tongue against the posterior pharyngeal wall during inspiration due to diminished tongue muscle activity. Apneas create asphyxia, which stimulates chemoreceptors and activates respiratory muscles, including the GG and HG. In anesthetized rats, multiple episodes of hypoxia produce a persistent increase in hypoglossal nerve activity, known as long-term facilitation (LTF). It has been hypothesized that LTF of hypoglossal nerve activity could play a compensatory role in OSA by increasing the tone of the muscles that control tongue position to maintain airway patency after successive apneic events. However, we have evidence to the contrary. Preliminary data show that asphyxia leads to a marked increase in drive to the tongue muscles, but also causes tongue muscle fatigue. We propose that the repeated, and progressively longer, pharyngeal airway occlusions that are observed in OSA patients during sleep are associated with asphyxia and LTF of tongue muscle activities. Accordingly, our overall hypothesis is that sustained asphyxia co-activates the retractor and protruder tongue muscles and causes tongue muscle fatigue, and that episodic asphyxia elicits LTF, which in turn exacerbates fatigue. We will measure the breath-by-breath changes in tongue force together with EMG activities of HG and GG muscles before, during, and after sustained and repeated episodes of asphyxia in anesthetized rats.